Recent studies have suggested that prostaglandins play a critical role in the impaired renal function of chronic liver disease. Zipser and Horton have demonstrated markedly increased urinary prostaglandin E excretion in patients with cirrhosis and ascites. Inhibition of prostaglandin production with anti-inflammatory drugs markedly impairs renal blood flow and glomerular filtration. In addition, preliminary studies by Zipser and Needleman have suggested that renal thromboxane A2 may mediate the intense renal vascular resistance in the animal ascites model. We propose that renal thromboxane A2 mediates the renal impairment and that prostaglandin E2 attenuates this vasoconstriction. The research objectives are to study the prostaglandin-thromboxane interactions with renal function in the experimental ascites model of thoracic vena caval constriction utilizing the isolated perfused rabbit kidney and prostaglandin bioassay cascade. Prostaglandin and thromboxane production will be quantitated by bioassay and validated by radiochemical techniques including 14C-arachidonate prelabeling and microsome incubation. In the human studies urinary prostaglandin E2 and F2alpha excretion will be measured from a large number of patients with acute and chronic liver failure including those with ascites, and those with the associated renal failure. The sequential pattern of prostaglandin excretion during the progression of hepatorenal syndrome will be analyzed. This work will 1) determine the presence of renal prostaglandin and thromboxane hypersecretion in the animal ascites model, 2) determine the effects of hormone stimulated prostaglandin and thromboxane synthesis on renal vascular resistance, 3) determine the prevalence and prognostic value of prostaglandin hypersecretion in patients with liver failure, and 4) ascertain the pattern of prostaglandin excretion during the course of hepatorenal failure.